A specific capture carrier for removing β-amyloid protein and its application

An amyloid-specific technology, applied in the direction of immunoglobulin, carrier-bound/immobilized peptide, anti-animal/human immunoglobulin, etc., can solve the problems of neuronal functional defects and the inability to realize Aβ peripheral clearance, etc., to achieve High drug stability, fast special equipment, effect of reducing burden

Active Publication Date: 2022-05-20
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The latest research shows that Aβ also has similar transmission activity to prions, and Aβ from peripheral sources injected into the tail vein can enter and deposit in the brain of WT mice, inducing Aβ plaque aggregation and pro-inflammatory factors (TNF-α and IL-6) expression, leading to neuronal functional deficits
The above studies show the importance and feasibility of Aβ peripheral clearance, but pure Aβ antibody cannot achieve pure Aβ peripheral clearance

Method used

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  • A specific capture carrier for removing β-amyloid protein and its application
  • A specific capture carrier for removing β-amyloid protein and its application
  • A specific capture carrier for removing β-amyloid protein and its application

Examples

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Effect test

example 1

[0038] Example 1: Adsorption of β-amyloid by MSNs and Ca-MOF / Ce-Mn MOF

[0039] 1.1. Synthesis of MSNs and Ca-MOF / Ce-Mn MOF

[0040] Synthesis of MSNs:

[0041] Mix 5mL of Cetyltrimethylammonium chloride (CTAC0.274mmol) and 5mL of triethanolamine (Triethanolamine, TEA 51.1mmol) with magnetic stirring and raise the temperature to 95°C. After 1h, 0.5mL of Ethyl orthosilicate (Tetraethylorthosilicate, TEOS 2.23mmol) was added dropwise and the temperature was maintained to continue magnetic stirring for 1h. Then, MSNs were obtained by centrifugation and washing with ethanol 3 times. The obtained MSNs were stirred in 1% hydrochloric acid ethanol solution at 60° C. for 3 h, repeated three times, and centrifuged to obtain the template removing agent CTAC-MSNs. Its transmission electron microscope image is shown in figure 2 Shown in Figure A.

[0042] Synthesis of Ce-Mn MOF:

[0043] Take 103.89g MnCl respectively 2 4H 2 O and 83.92 g CeCl 3 7H 2 O was dissolved in absolu...

example 2

[0049] Example 2: MSN S Clearance of β-amyloid protein in peripheral blood of APP / PS1 mice by -1F12 nanoparticle probe

[0050] 2.1. MSN S Preparation and detection of -1F12 nanoparticle probe

[0051] NHS modified MSNs: 5.4x 10 -6 mol NHS (NHS, N-hydroxysuccinimide, click chemical reaction with amino groups, used for bioconjugation and labeling) was added to 3 mL of CTAB-MSNs samples and reacted for 3 h; centrifuged, washed 3 times with PBS, dispersed in Store in 200 μL DI in the dark.

[0052] Coupling of 1F12 antibody: Mix MSNs-NHS and 1F12 antibody at a ratio of 10:3, and use 0.1M Na 2 CO 3 Adjust the pH value between 8.5 and 9.0, mix the two fully in the state of vortex, and incubate at 4°C for 3 to 5 hours; get MSN S -1F12 Nanoparticle Probe, MSN S -1F12 was dissolved in PBS at a concentration of 1 μg / μL for use; 1F12 was dissolved in PBS at a concentration of 1 μg / μL for use; MSNs-NHS was dissolved in PBS at a concentration of 1 μg / μL for use. MSNs and MSN S - ...

example 3

[0061] Example 3: HA-MSNs-1F12 Nanoparticle Probe Clearance of β-Amyloid in the Peripheral Blood and Brain of APP / PS1 Mice

[0062] 3.1. Preparation of HA-MSNs-1F12 functionalized nanoparticles

[0063] Fe 3 o 4 Preparation of @OA nanoparticles: monodisperse Fe 3 o 4 @OA nanoparticles were prepared by chemical co-precipitation method, under nitrogen flow, 6.56g FeCl 2 4H 2 O (33.5mmol) and 11.30g FeCl 3 6H 2 O (41.8 mmol) was dissolved in 80 mL of deionized (DI) water. The solution was heated to 80 °C and stirred vigorously for 0.5 h. 45 mL of ammonium hydroxide was added slowly and the resulting suspension was vigorously stirred for 5 min. 2 mL of OA was added and the mixture was kept at 80 °C for 25 min. The mixture was naturally cooled to room temperature. The black product was collected using a magnet and washed thoroughly with methanol and DI water to remove excess OA. The obtained oleic acid-stabilized monodisperse magnetic nanoparticles (Fe 3 o 4 @OA) dri...

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Abstract

The invention belongs to the field of biotechnology, and specifically relates to a specific capture carrier for removing β-amyloid protein and its application. The specific capture carrier is specifically a functional nanoparticle, including: mesoporous silica nanoparticles, Ca‑MOF, Ce‑Mn MOF, mesoporous silica nanoparticles functionalized with anti-hAβ1‑42 monoclonal antibody, and mediators functionalized with anti-hAβ1‑42 monoclonal antibody and hyaluronic acid that can cross the blood-brain barrier Porous silica nanoparticles. These functional nanoparticles can rapidly clear Aβ1–42 in the blood and even the brain, and can reshape the distribution of Aβ in the intestine by changing the metabolic pathway of the antibody, thereby alleviating the disease process of neurodegenerative diseases such as Alzheimer’s disease, compared with the control group Compared with APP / PS1 mice intravenously injected with antibody-functionalized nanoparticles, β-amyloid protein in peripheral blood and brain was significantly reduced, and cecum and colon β-amyloid protein was significantly increased. It has potential application value in the treatment of silent disease.

Description

technical field [0001] The invention belongs to the field of biotechnology, and more specifically relates to a specific capture carrier for removing beta-amyloid protein and its application. Background technique [0002] β-amyloid (amyloid-β, Aβ) deposition is the key pathological basis of cerebral amyloid angiopathy (Cerebral amyloidangiopathy, CAA) and Alzheimer's disease (Alzheimer's disease, AD). Clinical data show that 80%-98% of AD patients are accompanied by cerebrovascular dysfunction and CAA, and the deposition of Aβ on the cerebrovascular wall is positively correlated with the severity and progress of the disease. AD is the most common neurodegenerative disease leading to dementia. Deposition of Aβ in the extracellular space of the cerebral cortex and in the walls of cerebral vessels is a hallmark of AD neuropathology. Current studies suggest that excess Aβ production or defects in Aβ clearance play a critical or pathogenic role in AD pathogenesis. AD includes f...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K33/00A61K47/61A61K47/68A61P25/28B82Y5/00C07K16/18C07K17/14
CPCA61K33/00A61K47/68A61K47/61B82Y5/00A61P25/28C07K17/14C07K16/18C07K2317/92
Inventor 骆海明刘妮胡顺曹凯
Owner HUAZHONG UNIV OF SCI & TECH
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